Growth inhibition effects of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid on colorectal carcinoma cells and colon carcinoma-bearing mice

Autor: Qiong Wu, Yi Liu, Xuebao Zheng, Li Li, Kefeng Wu, Hua Ye, Xiaosheng Gao, Nianci Liang, Tu Yun, Meng Guo, Feng-Yan Yu, Yuzhen Zhu, Liao Cui, Yingnian Lv
Rok vydání: 2015
Předmět:
0301 basic medicine
Cyclin-Dependent Kinase Inhibitor p21
Cancer Research
Transplantation
Heterologous
Apoptosis
medicine.disease_cause
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Bcl-2-associated X protein
NF-KappaB Inhibitor alpha
Cell Line
Tumor
Survivin
Genetics
medicine
Animals
Humans
Molecular Biology
Cell Proliferation
bcl-2-Associated X Protein
Mice
Inbred BALB C
Mice
Inbred ICR
biology
Oncogene
Cell growth
Caspase 3
Cell cycle
Molecular biology
Antineoplastic Agents
Phytogenic
Up-Regulation
G2 Phase Cell Cycle Checkpoints
030104 developmental biology
Oncology
chemistry
Proto-Oncogene Proteins c-bcl-2
030220 oncology & carcinogenesis
Colonic Neoplasms
biology.protein
Molecular Medicine
Female
Growth inhibition
Carcinogenesis
Colorectal Neoplasms
Diterpenes
Kaurane
Zdroj: Molecular medicine reports. 13(4)
ISSN: 1791-3004
Popis: The aim of the present study was to investigate the mechanism underlying the antitumor effects of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) in colorectal cancer (CRC). 5F was isolated and used to treat C26 murine colon carcinoma cells, a xenograft tumor mouse model (induced by C26 cells) and a CRC mouse model [induced by 1,2-dimethylhydrazine (DMH)/dextran sodium sulfate (DSS)]. C26 cell growth was inhibited by 5F in a dose- and time-dependent manner in vitro. In addition, 5F induced cell apoptosis and cell cycle arrest in the G2 phase, increased the activity of caspase-3 and caspase-9, but did not affect the activity of cascase‑8, suggesting that 5F induced apoptosis via activation of the mitochondrial signaling pathway rather than the death‑receptor signaling pathway. Furthermore, treatment of C26 cells with 5F resulted in upregulation of cyclin‑dependent kinase inhibitor 1A (p21, Cip1), Bcl‑2‑associated X protein, nuclear factor of κ light polypeptide gene enhancer in B‑cells inhibitor, α and downregulation of B‑cell lymphoma 2, nuclear factor κ‑light‑chain enhancer of activated B cells and survivin. In vivo animal models demonstrated that 5F treatment protected mice from carcinogenesis induced by DMH/DSS and markedly decreased the xenograft tumor weight with minimal side effects. Therefore, 5F may have potential as an anti-CRC therapeutic agent for use in the clinical setting.
Databáze: OpenAIRE
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